反应详情

温度

100 °C

To a stirred and chilled (0° C.) suspension of 2-methyl-2H-indazol-6-ylamine (1.52 g) in DCE (6 mL), under nitrogen, was added trimethylaluminium (2M solution in toluene, 5 mL, 9.37 mmol). This mixture was added dropwise to a stirred and chilled (0° C.) solution of 2-[(2-chloro-pyridin-4-ylmethyl)-amino]-nicotinic acid methyl ester (1.45 g, 5.21 mmol) in DCE (14.7 mL). The mixture was heated at 100° C. for 2 hours before cooling to room temperature and quenching by pouring into aqueous sodium-potassium tartrate solution. The mixture was extracted with EtOAc and the combined organic layers washed successively with dilute aqueous citric acid solution, dilute aqueous sodium hydrogen carbonate solution and brine, dried and concentrated in vacuo to give 2-[(2-chloro-pyridin-4-ylmethyl)-amino]-N-(2-methyl-2H-indazol-6-yl)-nicotinamide (1.58 g); 1H-NMR (300 MHz, d6-DMSO) 10.26 (1H, s), 8.40 (1H, t), 8.28 (1H, d), 8.25 (1H, s), 8.06-8.12 (3H, m), 7.62 (1H, d), 7.35 (1H, s), 7.30 (1H, unresolved dd), 7.27 (1H, unresolved dd), 6.68 (1H, dd), 4.67 (2H, d), 4.10 (3H, s).

1. temperaturechilled
2. additionThis mixture was added dropwise to
3. stirringa stirred
4. temperaturebefore cooling to room temperature
5. customquenching
6. additionby pouring into aqueous sodium-potassium tartrate solution
7. extractionThe mixture was extracted with EtOAc
8. washthe combined organic layers washed successively with dilute aqueous citric acid solution, dilute aqueous sodium hydrogen carbonate solution and brine
9. customdried
10. concentrationconcentrated in vacuo